PROJECT SUMMARY (Overall Component) Structural biology is a multidisciplinary research area that focuses on the important relationship between macromolecular structure and function. The Oklahoma Center of Biomedical Research Excellence (COBRE) in Structural Biology (OCSB) was established in 2012 with Phase I funding. The OCSB supports faculty research projects and three core facilities on the OU-Norman and OU Health Sciences Center campuses for crystallization of macromolecules of biomedical importance, X-ray data collection, protein expression and purification and biophysical analysis. Structural biology lies at the intersection of many different areas of biological sciences and thus has the potential of impacting numerous biomedically important fields. The research projects proposed herein have direct relevance to human diseases and conditions associated with neurodegenerative diseases, cancer, stroke, and both chronic and acute bacterial infections. The overall objective of this Phase II application is to continue to build and nurture a critical mass of researchers in structural biology and support their research programs through shared resources and expertise. The specific aims of this Phase II application are to: 1) Support and augment the research activities and career development of junior and early career investigators through senior mentorship and enhanced research infrastructure with the goal of enhancing their ability to compete successfully for independent external funding; 2) Continue to provide state-of-the-art research core facilities in support of structural biology researchers by expanding the capabilities of these cores and developing a path to self-sustainability; and 3) Continue to promote and enhance the visibility of structural biology in the State of Oklahoma through OCSB-sponsored activities such as annual symposia, workshops, a pilot project program, and undergraduate and graduate research and education programs.